Optical tomographic imaging uses signals from the amplitude attenuation or phase modification of light scattered by a tissue or sample. Injected light diffuses throughout a target and exits at the surface. Light can be injected and received at multiple positions on a surface of a target material, such as body structure, and the received light used to generate tomographic images. Amplitude attenuation and phase shift of the received light relative to the injected light can be used to resolve spatial information regarding the absorbing and scattering media in the target, for example, the spatial information can be presented in the form of a volumetric or cross-sectional image of the anatomy of a body part.
Peripheral Arterial Disease (PAD) is a highly prevalent atherosclerotic syndrome that affects approximately 8 to 12 million individuals in the United States and is associated with significant morbidity and mortality. PAD is responsible for approximately 275,000 hospital admissions per year, as well as over 2,750,000 office visits per year and approximately 45,000 deaths per year. PAD results from a variable combination of changes in the intima of arteries consisting of focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue, calcium deposits. PAD also results from a build-up of plaque on the inside of the arterial walls, inhibiting proper blood supply to organs. The prevalence of PAD increases significantly with age. In a large study that included 5,450 patients, the prevalence of PAD based on the ankle-brachial index (ABI) increased from 9% of subjects 55-59 years of age to 57% of patients 85-89 years of age. The prevalence of PAD does not change with the patient's gender.
PAD typically manifests itself early in the legs and foot and is commonly referred to as lower extremity arterial disease (LEAD). Lower extremity arterial disease (LEAD) is defined as decreased arterial perfusion to the lower extremities. LEAD is a common condition in individuals with diabetes. LEAD in diabetes is compounded by the presence of peripheral neuropathy and by susceptibility to infection. Peripheral neuropathy causes a lack of sensation in the upper and lower peripheries leading to a patient's inability to feel cuts and bruises. Infections are thus more likely to occur.
If undetected, LEAD can progress to cause foot ulcerations, poor wound healing, gangrene, and ultimately amputation. Detection of LEAD is difficult, especially in patients with diabetes where calcification of the arteries and neuropathy alter the blood pressure measurements. The current techniques used to diagnose LEAD, such as the ankle-brachial index (ABI), typically use compressible arteries in order to accurately detect LEAD, complicating diagnosis in many patients. Currently the standard for identifying and treating occlusive LEAD in the arterial system is Digital Subtraction Angiography (DSA).
In DSA a contrast agent is injected intra-arterially to the patient and an image of the vasculature is obtained. However, this method of imaging is invasive and contrast media is nephrotoxic and therefore hazardous in patients with significant medical co-morbidities. In addition, the patient is exposed to ionizing radiation, which limits DSA's frequency of use. Peripheral vascular measures used to assess LEAD are usually derived from non-imaging techniques. Palpation of the peripheral pulses has been used as a clinical tool to assess occlusive LEAD in patients. However, the subjective nature of this method can lead to inconsistency amongst physician evaluations. Factors such as temperature, anatomical variation and the physician's palpation technique can greatly alter the diagnosis. Some physicians also use pressure cuffs to determine arterial blood pressure.
LEAD can also be assessed with invasive procedures. For example, the use of arterial catheters for blood pressure monitoring. Although these methods are sensitive and accurate, invasive methods tend to be more cumbersome to use, and they generally bear greater risk of adverse effects relative to non-invasive techniques. These factors alongside the higher cost, limit the use of invasive techniques as a screening tool.
Measurement of the ankle brachial index (ABI) which is the ratio of systolic pressure measured at the dorsalis pedis or posterior tibial artery to the brachial systolic pressure is also used to evaluate LEAD. However, the progression of LEAD in diabetes patients is frequently compounded by neuropathy and heavy calcification of the arteries that renders them non-compressible. Furthermore, blood pressure readings at the dorsalis pedis are often faint or in some cases absent. Pulse volume recordings (PVR) utilize blood pressure cuffs inflated to 60 mmHg and are placed at the thigh, calf, and forefoot level, and the volume of expansion and contraction of the extremity is measured in order to accurately gauge the amount of blood entering the extremity during the cardiac cycle. In the setting of arterial stenosis, PVR waveforms will be diminished and this measuring tool is used to complement ABI in patients with diabetes. However, PVR provides a more subjective rather than objective measure of the degree of arterial insufficiency.
LEAD can also be diagnosed using imaging methods such as velocimetry and continuous-wave Doppler ultrasound. The Doppler waveform obtained from a normal artery has a triphasic shape. However, measuring at an occluded location shows a waveform of increased velocity and bi- or monophasic behavior. Unlike ABI, and TSP, velocimetry only provides a qualitative measure of occlusive LEAD in compressible arteries. In addition, Doppler ultrasound cannot be used on patients with diabetes and non-compressible arteries because the pressures obtained in these patients are spuriously high. Due to the shortcomings of continuous wave Doppler ultrasound and ABI/PVR, Duplex Ultrasound is frequently used to analyze the peripheral vasculature. Duplex Ultrasound is a combination conventional B-mode ultrasound imaging with color Doppler and pulsed-wave Doppler waveform sampling. The limitations of duplex are that it fails to visualize up to 13% of arterial segments in the calf and is operator dependent.
Thus, while X-ray and MRI provide great anatomical detail they typically do not provide enough physiological detail and smaller arteries may not be visualized or the artery may not have as much blood flow as expected.